Differential diagnosis of Huntington's disease- neurological aspects of NKX2-1-related disorders.

Benign hereditary chorea (BHC) is an inherited neurological disorder consisting of childhood-onset, nonprogressive chorea, generally without any other manifestations. In most reported cases, the inheritance of BHC is autosomal dominant but both incomplete penetrance and variable expressivity are observed and can be caused by NKX2-1 mutations. The spectrum contains choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome. The neurological symptoms can be misdiagnosed as Huntington's disease (HD). The two Polish families were diagnosed with NKX2-1 gene mutations and a literature review concerning the NKX2-1-related disorders was conducted. All family members were examined by experienced movement disorders specialists. PubMed database was searched to obtain previously described NKX2-1 cases. Whole exome sequencing (WES) was performed in one proband (Family A) and direct NKX2-1 sequencing in the second (Family B). Two Polish families were diagnosed with NKX2-1 gene mutations (p.Trp208Leu and p.Cys117Alafs*8). In one family, the co-occurrence of HD was reported. Forty-nine publications were included in the literature review and symptoms of 195 patients with confirmed NKX2-1 mutation were analyzed. The most common symptoms were chorea and choreiform movements, and delayed motor milestones. The NKX2-1 mutation should always be considered as a potential diagnosis in families with chorea, even with a family history of HD. Lack of chorea does not exclude the NKX2-1-related disorders.

The Role of MicroRNAs in Progressive Supranuclear Palsy-A Systematic Review.

Progressive supranuclear palsy (PSP) is a rare, neurodegenerative movement disorder. Together with multiple system atrophy (MSA), Dementia with Lewy bodies (DLB), and corticobasal degeneration (CBD), PSP forms a group of atypical parkinsonisms. The latest diagnostic criteria, published in 2017 by the Movement Disorders Society, classify PSP diagnosis into defined, probable, and possible categories based on clinical examination. However, no single test is specific and sensitive for this disease. Microribonucleic acids (miRNAs) are promising molecules, particularly in the case of diseases that lack appropriate diagnostic and treatment tools, which supports exploring their role in PSP. We aimed to systematically review the current knowledge about the role of miRNAs in PSP. This study was registered in the Open Science Framework Registry, and the protocol is available online. Primary original studies, both clinical and preclinical, written in English and assessing miRNAs in PSP were included. Systematic reviews, meta-analyses, reviews, case reports, letters to editors, commentaries, conference abstracts, guidelines/statements, expert opinions, preprints, and book chapters were excluded. The following five databases were searched: Embase, Medline Ultimate, PubMed, Scopus, and Web of Science. Each database was last searched on 18 June 2024. Eventually, nine original studies relevant to the discussed area were included. The risk of bias was not assessed. The selected research suggests that miRNAs may be considered promising biomarkers in PSP. However, the exact involvement of miRNAs in the pathogenesis of PSP is still to be determined. Several microRNAs were found to be dysregulated in patients with PSP. This applies to both brain tissue and fluids like cerebrospinal fluid CSF or blood. Several miRNAs were found that could potentially be helpful in differentiating among PSP patients, PD patients, and healthy individuals. Although some correlations and alterations have already been found, this field requires much more research. MicroRNAs are exciting and promising small molecules, and their investigation into many diseases, including PSP, may lead to significant discoveries.

Exploring Fecal Microbiota Transplantation for Modulating Inflammation in Parkinson's Disease: A Review of Inflammatory Markers and Potential Effects.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by numerous motor and non-motor symptoms. Recent data highlight a potential interplay between the gut microbiota and the pathophysiology of PD. The degeneration of dopaminergic neurons in PD leads to motor symptoms (tremor, rigidity, and bradykinesia), with antecedent gastrointestinal manifestations, most notably constipation. Consequently, the gut emerges as a plausible modulator in the neurodegenerative progression of PD. Key molecular changes in PD are discussed in the context of the gut-brain axis. Evidence suggests that the alterations in the gut microbiota composition may contribute to gastroenteric inflammation and influence PD symptoms. Disturbances in the levels of inflammatory markers, including tumor necrosis factor-α (TNF α), interleukin -1ß (IL-1ß), and interleukin-6 (IL-6), have been observed in PD patients. These implicate the involvement of systemic inflammation in disease pathology. Fecal microbiota transplantation emerges as a potential therapeutic strategy for PD. It may mitigate inflammation by restoring gut homeostasis. Preclinical studies in animal models and initial clinical trials have shown promising results. Overall, understanding the interplay between inflammation, the gut microbiota, and PD pathology provides valuable insights into potential therapeutic interventions. This review presents recent data about the bidirectional communication between the gut microbiome and the brain in PD, specifically focusing on the involvement of inflammatory biomarkers.

ADCY5-related dyskinesia - case series with literature review.

INTRODUCTION: ADCY5-related dyskinesia is a rare neurological disease caused by mutations in the gene encoding the adenylyl cyclase 5 (ADCY5) isoform, a protein that plays an important role in intracellular transmission. Variants in ADCY5 are associated with a spectrum of neurological disease encompassing dyskinesia, chorea, and dystonia. State of the-art. ADCY5 mutations result in clinically heterogeneous manifestations which comprise a range of core and less to highly variable symptoms. Due to the heterogeneous nature and difficulty in diagnosis of the disorder, available treatments are highly limited. CLINICAL IMPLICATIONS: ADCY5-related dyskinesia was reported in 52 individuals in the literature over a five-year period (January 2017 to January 2022). We have listed all the symptoms and their frequency. The most common symptom reported in these patients was dystonia. Over 50% of patients developed dyskinesia and chorea. We report two cases of familial occurrence of symptomatic ADCY5-related dyskinesia. A 45-year-old patient presented with involuntary movements which had been occurring since childhood. The proband's neurological examination revealed dysarthria, involuntary myoclonic twitches, and choreic movements. The patient's 9-year-old son had developed involuntary movements, mainly chorea and dystonia. FUTURE DIRECTIONS: This paper aims to summarise the recent literature on ADCY5-related neurological disorders and to present a new case of a Polish family with ADCY5 mutation. Genetic diagnostics are important in the context of possible future targeted treatments.

Validation of Polish version of Gastrointestinal Dysfunction Scale for Parkinson's Disease.

AIM OF STUDY: The Gastrointestinal Dysfunction Scale for Parkinson's Disease (GIDS-PD) is a novel, disease-specific self-report questionnaire used to quantitatively assess features of gastrointestinal dysfunction symptoms in patients with Parkinson's Disease. The aim of this paper was to validate the Polish translation of the scale, to summarise its consistency with the English language version, and to assess its clinimetric properties. CLINICAL RATIONALE FOR STUDY: Gastrointestinal dysfunction is a common and often debilitating manifestation of Parkinson's Disease (PD). Gastrointestinal symptoms are also considered to be prodromal features of this disease. To date, there has been no scale in Polish that has precisely assessed gastrointestinal symptoms in patients with PD. MATERIAL AND METHODS: The GIDS-PD was translated into Polish by two investigators (M.K. and J.N.). A back-translation was completed by two separate investigators (M.F. and A.A.) who were not involved in the original translation. Afterwards, 10 Polish PD patients underwent cognitive pre-testing. After the final translation was officially approved by the Movement Disorder Society, it was tested on 64 individuals with PD during field testing. For the purpose of testing scale reliability, 20 of the patients recruited for field testing underwent the GIDS-PD for a second time after 8-12 weeks. RESULTS: The GIDS-PD demonstrated overall good consistency (Cronbach's alpha of 0.74, ICC of 0.74). Regarding the individual domains, the constipation subscore demonstrated good reliability, the bowel irritability subscore demonstrated moderate reliability, and the upper GI subscore demonstrated poor reliability. Upper GI symptoms seem to be less pronounced, and also more varied, in the Polish PD population than in its English language counterpart. CONCLUSIONS AND CLINICAL IMPLICATIONS: This paper provides a validated Polish translation of the GIDS-PD questionnaire. We highly recommend using the GIDS-PD for research purposes, as well as everyday clinical practice in the Polish PD population.

Unilateral gamma knife thalamotomy for tremor safety and efficacy in multimodal assessment: a prospective case-control study with two-year follow-up.

INTRODUCTION: Unilateral gamma knife thalamotomy (GKT) is a treatment option for pharmacoresistant tremor of various aetiologies. There have been to date no randomised controlled trials performed to assess its safety and efficacy. Our aim was to summarise a two-year multimodal observation of patients with tremor caused by Parkinson's Disease (PD) or essential tremor (ET). MATERIAL AND METHODS: 23 patients with PD (n = 12) or ET (n = 11) were included. They underwent assessments before, V0 (n = 23), and 12 months, V12 (n = 23), and 24 months, V24 (n = 15), after unilateral GKT. Patients were assessed with psychological tests and acoustic voice analysis. Tremor assessment was performed with a digitising table using the Fahn-Tolosa-Marin rating scale (FTMRS). The Unified Parkinson's Disease rating scale part III (UPDRS-III) was also used in the PD group. Gait and balance was assessed using clinical tests, stabilometric platform, and treadmill. RESULTS: No side effects were observed in a two-year follow-up. There was no notable deterioration observed in the patients' psychological evaluation, speech, or assessment of gait and balance. The scores were significantly lower (p = 0.01) in parts A and B of FTMRS one year after GKT. In post hoc analysis, the scores did not differ significantly between V0 and V24. In FTMRS part C (activities of daily living), no significant change was observed. There was no significant difference in total UPDRS part III score or in score of UPDRS part III domains 3 and 4 ('tremor at rest' and 'action and postural tremor of hands') between measurements. CONCLUSIONS: UGKT may be a safe treatment modality if performed in an experienced centre. Tremor reduction may diminish over time, and UGKT did not lead to cognitive, gait or speech deterioration in a long-term observation.

Machine Learning and Eye Movements Give Insights into Neurodegenerative Disease Mechanisms.

Humans are a vision-dominated species; what we perceive depends on where we look. Therefore, eye movements (EMs) are essential to our interactions with the environment, and experimental findings show EMs are affected in neurodegenerative disorders (ND). This could be a reason for some cognitive and movement disorders in ND. Therefore, we aim to establish whether changes in EM-evoked responses can tell us about the progression of ND, such as Alzheimer's (AD) and Parkinson's diseases (PD), in different stages. In the present review, we have analyzed the results of psychological, neurological, and EM (saccades, antisaccades, pursuit) tests to predict disease progression with machine learning (ML) methods. Thanks to ML algorithms, from the high-dimensional parameter space, we were able to find significant EM changes related to ND symptoms that gave us insights into ND mechanisms. The predictive algorithms described use various approaches, including granular computing, Naive Bayes, Decision Trees/Tables, logistic regression, C-/Linear SVC, KNC, and Random Forest. We demonstrated that EM is a robust biomarker for assessing symptom progression in PD and AD. There are navigation problems in 3D space in both diseases. Consequently, we investigated EM experiments in the virtual space and how they may help find neurodegeneration-related brain changes, e.g., related to place or/and orientation problems. In conclusion, EM parameters with clinical symptoms are powerful precision instruments that, in addition to their potential for predictions of ND progression with the help of ML, could be used to indicate the different preclinical stages of both diseases.

Glymphatic System and Mitochondrial Dysfunction as Two Crucial Players in Pathophysiology of Neurodegenerative Disorders.

Neurodegenerative diseases are a complex problem affecting millions of people around the world. The pathogenesis is not fully understood, but it is known that both insufficiency of the glymphatic system and mitochondrial disorders affect the development of pathology. It appears that these are not just two independent factors that coexist in the processes of neurodegeneration, but that they often interact and drive each other. Bioenergetics disturbances are potentially associated with the accumulation of protein aggregates and impaired glymphatic clearance. Furthermore, sleep disorders characteristic of neurodegeneration may impair the work of both the glymphatic system and the activity of mitochondria. Melatonin may be one of the elements linking sleep disorders with the function of these systems. Moreover, noteworthy in this context is the process of neuroinflammation inextricably linked to mitochondria and its impact not only on neurons, but also on glia cells involved in glymphatic clearance. This review only presents possible direct and indirect connections between the glymphatic system and mitochondria in the process of neurodegeneration. Clarifying the connection between these two areas in relation to neurodegeneration could lead to the development of new multidirectional therapies, which, due to the complexity of pathogenesis, seems to be worth considering.

Clinical Phenotypes of Progressive Supranuclear Palsy-The Differences in Interleukin Patterns.

Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome based on tau pathology; its clinical phenotype differs, but PSP with Richardson's syndrome (PSP-RS) and the PSP parkinsonism predominant (PSP-P) variant remain the two most common manifestations. Neuroinflammation is involved in the course of the disease and may cause neurodegeneration. However, an up-to-date cytokine profile has not been assessed in different PSP phenotypes. This study aimed to evaluate possible differences in neuroinflammatory patterns between the two most common PSP phenotypes. Serum and cerebrospinal fluid (CSF) concentrations of interleukin-1 beta (IL-1ß) and IL-6 were analyzed using enzyme-linked immunosorbent assay (ELISA) kits in 36 study participants-12 healthy controls and 24 patients with a clinical diagnosis of PSP-12 PSP-RS and 12 PSP-P. Disease duration among PSP patients ranged from three to six years. All participants underwent basic biochemical testing, and neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values were calculated. Due to a lack of neuropathological examinations, as all patients remain alive, total tau levels were assessed in the CSF. Tau levels were significantly higher in the PSP-P and PSP-RS groups compared to the healthy controls. The lowest concentrations of serum and CSF interleukins were observed in PSP-RS patients, whereas PSP-P patients and healthy controls had significantly higher interleukin concentrations. Furthermore, there was a significant correlation between serum IL-6 levels and PLR in PSP-RS patients. The results indicate the existence of distinct neuroinflammatory patterns or a neuroprotective role of increased inflammatory activity, which could cause the differences between PSPS phenotypes and clinical course. The causality of the correlations described requires further studies to be confirmed.

Cathepsin B p.Gly284Val Variant in Parkinson's Disease Pathogenesis.

Parkinson's disease (PD) is generally considered a sporadic disorder, but a strong genetic background is often found. The aim of this study was to identify the underlying genetic cause of PD in two affected siblings and to subsequently assess the role of mutations in Cathepsin B (CTSB) in susceptibility to PD. A typical PD family was identified and whole-exome sequencing was performed in two affected siblings. Variants of interest were validated using Sanger sequencing. CTSB p.Gly284Val was genotyped in 2077 PD patients and 615 unrelated healthy controls from the Czech Republic, Ireland, Poland, Ukraine, and the USA. The gene burden analysis was conducted for the CTSB gene in an additional 769 PD probands from Mayo Clinic Florida familial PD cohort. CTSB expression and activity in patient-derived fibroblasts and controls were evaluated by qRT-PCR, western blot, immunocytochemistry, and enzymatic assay. The CTSB p.Gly284Val candidate variant was only identified in affected family members. Functional analysis of CTSB patient-derived fibroblasts under basal conditions did not reveal overt changes in endogenous expression, subcellular localization, or enzymatic activity in the heterozygous carrier of the CTSB variant. The identification of the CTSB p.Gly284Val may support the hypothesis that the CTSB locus harbors variants with differing penetrance that can determine the disease risk.

Cannabis in Parkinson's Disease - the patient's perspective versus clinical trials: a systematic literature review.

Cannabis and cannabinoids are often considered in the treatment of Parkinson's Disease (PD). The purpose of this paper was to perform a systematic review of the available data on cannabis treatment. We aimed to assess randomised trials as well as surveys among patients. We identified 569 papers on PD and cannabinoid treatment. Of these, there were only seven papers featuring randomised trials on the effects of different cannabinoids on PD. The results of these trials did not support the efficacy of cannabinoids in the treatment of motor signs of PD. Based on the available data, we conclude that there is currently insufficient data to support the administration of cannabinoids to PD patients. Larger, randomised studies of cannabis use in PD should be conducted.

Platelet-to-lymphocyte ratio and neutrophil-tolymphocyte ratio may reflect differences in PD and MSA-P neuroinflammation patterns.

AIM OF THE STUDY: To assess the usefulness of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in evaluating the inflammatory process in alpha-synucleinopathies. CLINICAL RATIONALE FOR THE STUDY: The role of neuroinflammation in PD and MSA pathogenesis is indisputable. However, there is no method available in everyday use that would enable its evaluation. We suggest that NLR and PLR, as non-specific parameters of inflammation, due to its approachability could be helpful in the assessment of inflammatory activity in alpha-synucleinopathies in everyday clinical practice. MATERIAL AND METHODS: 98 patients with a clinical diagnosis of PD, 28 with MSA-P, and 99 healthy age-matched controls, were included in the study. Blood samples were analysed in order to count neutrophil and lymphocyte rates and, subsequently, NLR and PLR. The obtained parameters were compared between the groups. Results were statistically analysed. RESULTS: Our results indicate that patients with PD have higher values of NLR and PLR compared to controls. For MSA-P, only NLR was significantly higher in relation to the control group. There were no statistically significant differences between patients with PD and MSA-P in relation to NLR and PLR values. There was a positive average correlation between NLR and disease duration for MSA-P patients. CONCLUSIONS: NLR and PLR values are significantly higher in alpha-synucleinopathies (MSA-P and PD) in relation to a control group. In PD patients, both NLR and PLR values are significantly higher in relation to a control group, whereas in patients with MSA-P, only NLR is significantly increased. The observed differences may reflect distinct neuroinflammatory patterns present in these entities. CLINICAL IMPLICATIONS: NLR and PLR are features of peripheral inflammation. Their specificity is relatively low, although increased values suggest possible inflammatory pathogenesis of clinical entities. NLR is based on the observations that in chronic and acute diseases the neutrophil rate has a tendency to rise, while the lymphocyte rate tends to decline. This aspect of inflammatory processes has been primarily evaluated in Intensive Care Units. PLR is a marker presenting changes in platelet and lymphocyte counts caused by acute inflammatory or prothrombotic states. Different values of NLR and PLR in PD and MSA-P compared to healthy controls suggest that in these two alpha-synucleinopathies, different patterns of neuroinflammation might be present. The role of inflammation in the differential diagnosis of parkinsonian syndromes remains unexplored.

Carbohydrate metabolism and lipid profile in patients with Parkinson's disease with subthalamic deep brain stimulation.

AIM OF THE STUDY: Assessment of potential effect of subthalamic nucleus deep brain stimulation (STN-DBS) on glucose metabolism in patients with Parkinson's disease (PD). CLINICAL RATIONALE FOR THE STUDY: Although a valuable alternative to pharmacotherapy in advanced PD, STN-DBS is thought to negatively affect the cardiometabolic profile of patients (including body mass, lipid profile). Exacerbation of glucose metabolism dysregulation after DBS could therefore be assumed. MATERIAL AND METHODS: Two groups of patients with Parkinson's disease were included: 20 treated pharmacologically (PHT) and 20 newly qualified for STN-DBS (DBS) - with the first assessment prior to surgery, and the second 11 months after surgery on average. Body mass index (BMI), plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and glucose levels during a three-point oral glucose tolerance test were measured three times (median intervals between visits 12 and 14 months respectively). RESULTS: Significant differences between the two groups were noted with respect to changes in BMI, and serum concentration of TG and HDL-C over the course of the study. In the DBS group, a significant increase in BMI (26.42 vs. 27.24 kg/m2, p = 0.03) and TG level (103.8 vs. 142.8 mg/dL, p < 0.001) with a simultaneous decrease in HDL-C level (54.4 vs. 46 mg/dL, p < 0.01) was observed. Mean glucose level after oral glucose administration was lower in the DBS than in the PHT group (147.4 vs. 120.2 mg/dL, p = 0.03 after one hour and 109.9 vs. 82.3 mg/dL, p < 0.01 after two hours) during the second visit. Also inter-visit changes in fasting glucose levels (8.4 mg/dL in the PHT group and -5.8 mg/dL in the DBS group, p = 0.02) differed over the study duration. CONCLUSIONS: Our observations are similar to previous ones indicating less favourable changes in BMI and some lipid fractions in patients treated surgically. Interestingly, such a trend was not observed for glucose metabolism parameters, suggesting that mechanisms other than simple body mass changes are involved in early biochemical changes after STN-DBS in PD patients. CLINICAL IMPLICATIONS: The metabolic consequences of DBS require further investigation as an additional factor potentially affecting the outcome of therapy, and routine patient follow-up should not be limited to neurological and psychological assessments.

C9orf72 hexanucleotide repeat expansion found in suspected spinobulbar muscular atrophy (SBMA).

INTRODUCTION: The expansion of a hexanucleotide GGGGCC repeat (G4C2) in the C9orf72 locus is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In addition, C9orf72 expansion has also been detected in patients with a clinical manifestation of Parkinson's Disease (PD), Alzheimer's Disease (AD), Huntington's Disease (HD), and ataxic disorders. MATERIAL AND METHODS: A total of 1,387 patients with clinically suspected ALS, HD or spinal and bulbar muscular atrophy (SBMA) were enrolled, and the prevalence of C9orf72 expansions was estimated. RESULTS: The hexanucleotide expansion accounted for 3.7% of the ALS patients, 0.2% of the HD suspected patients with excluded HTT mutation, and 1.3% of the suspected SBMA patients with excluded mutation in AR gene. CONCLUSIONS: This is the first report revealing the presence of C9orf72 expansion in patients with a suspected SBMA diagnosis. Consequently, we advise testing for C9orf72 expansion in patients presenting with the SBMA phenotype and a genetically unsolved diagnosis.

Frequency of spinocerebellar ataxia mutations in patients with multiple system atrophy.

PURPOSE: Investigate single nucleotide variants and short tandem repeats in 39 genes related to spinocerebellar ataxia in clinical and pathologically defined cohorts of multiple system atrophy. METHODS: Exome sequencing was conducted in 28 clinical multiple system atrophy patients to identify single nucleotide variants in spinocerebellar ataxia-related genes. Novel variants were validated in two independent disease cohorts: 86 clinically diagnosed multiple system atrophy patients and 166 pathological multiple system atrophy cases. Expanded repeat alleles in spinocerebellar ataxia genes were evaluated in 36 clinically diagnosed multiple system atrophy patients, and CAG/CAA repeats in TATA-Box Binding Protein (TBP, causative of SCA17) were screened in 216 clinical and pathological multiple system atrophy patients and 346 controls. RESULTS: No known pathogenic spinocerebellar ataxia single nucleotide variants or pathogenic range expanded repeat alleles of ATXN1, ATXN2, ATXN3, CACNA1A, AXTN7, ATXN8OS, ATXN10, PPP2R2B, and TBP were detected in any clinical multiple system atrophy patients. However, four novel variants were identified in four spinocerebellar ataxia-related genes across three multiple system atrophy patients. Additionally, four multiple system atrophy patients (1.6%) and one control (0.3%) carried an intermediate length 41 TBP CAG/CAA repeat allele (OR = 4.11, P = 0.21). There was a significant association between the occurrence of a repeat length of longer alleles (> 38 repeats) and an increased risk of multiple system atrophy (OR = 1.64, P = 0.03). CONCLUSION: Occurrence of TBP CAG/CAA repeat length of longer alleles (> 38 repeats) is significantly associated with increased multiple system atrophy risk. This discovery warrants further investigation and supports a possible genetic overlap of multiple system atrophy with SCA17.

Botulinum toxin type-A preparations are not the same medications - basic science (Part 1).

Botulinum neurotoxin type A (BoNT/A) formulations are widely used in clinical practice. Although they share a common mechanism of action resulting in presynaptic block in acetylocholine release, their structure and pharmacological properties demonstrate some similarities and many differences. Bioequivalence has been discussed since the onset of the clinical use of BoNT/A. In this review, we provide an update on the studies and compare the molecular structure, mechanisms of action, diffusion and spread, as well as immunogenicity and dose equivalence of onabotulinumtoxinA, abobotulinumtoxinA and incobotulinumtoxinA.

Botulinum toxin type-A preparations are not the same medications - clinical studies (Part 2).

The growing number of Botulinum neurotoxin type A (BoNT/A) preparations on the market has resulted in a search for pharmacological, clinical and pharmacoeconomic differences. Patients are occasionally switched from one botulinum toxin formulation to another. The aim of this paper was to review studies that have made direct comparisons of the three major BoNT/A preparations presently on the market: ona-, abo- and incobotulinumtoxinA. We also review the single medication Class I pivotal and occasionally Class II-IV studies, as well as recommendations and guidelines to show how effective doses have been adopted in well-established indications such as blepharospasm, hemifacial spasm, cervical dystonia and adult spasticity. Neither direct head-to-head studies nor single medication studies between all preparations allow the formation of universal conversion ratios. All preparations should be treated as distinct medications with respect to their summary of product characteristics when used in everyday practice.

Movement disorders associated with chromosomal aberrations diagnosed in adult patients.

INTRODUCTION: Chromosomal aberrations are rare but important causes of various movement disorders. In cases of movement disorders associated with dysmorphic features, multiorgan involvement and/or intellectual disability, the identification of causative chromosomal aberrations should be considered. AIM OF THE STUDY: The purpose of this article was to summarise clinical findings in six patients with dystonia and two with parkinsonism and identified chromosomal aberrations in a single-centre prospective study. MATERIALS AND METHODS: 15 adult patients with dystonia or parkinsonism were referred to array comparative genomic hybridisation (aCGH) testing from our Department of Neurology between 2014 and 2019. Additionally, one patient had a karyotype examination. Detailed clinical, psychological and radiological diagnostics were performed in each case. RESULTS: Chromosomal aberrations were identified in six patients with dystonia and two with parkinsonism. Two patients were identified with aberrations associated with de Grouchy syndrome. We also reported generalised dystonia in patients with deletion in 3q26.31 and duplication in 3p26.3, as well as dystonia and hypoacusis in a patient with duplication in Xq26.3. One patient was diagnosed with duplication in 21q21.1. Early-onset parkinsonism was a manifestation of deletion in the 2q24.1 region. Late onset parkinsonism was also present in the patient with the most severe aberrations (duplication 1q21.1q44; deletion 10p15.3p15.1; deletion 10q11.21). CONCLUSIONS: Dystonia and parkinsonism are possible manifestations of chromosomal aberrations. Chromosomal aberrations should be excluded in patients with early-onset movement disorders and concomitant dysmorphic features and/or intellectual disability. It is important to include this cause of movement disorders in future classifications. aCGH can be a valuable diagnostic tool in the evaluation of movement disorder aetiology.

Genetics of Parkinson's disease in the Polish population.

INTRODUCTION: Genetic forms of Parkinson's disease (PD) often cluster in different ethnic groups and may present with recognisable unique clinical manifestations. Our aim was to summarise the current state of knowledge regarding the genetic causes of PD and describe the first Polish patient with SNCA duplication. METHODOLOGY: We searched the electronic database, PubMed, for studies between January 1995 and June 2020 that evaluated genetics in Polish patients with PD, using the search terms 'Parkinson's disease, 'Polish', 'genetics', 'mutations', and 'variants'. RESULTS: In total, 73 publications were included in the review; 11 genes responsible for monogenic forms and 19 risk factor genes have been analysed in the Polish population. Pathogenic variants were reported in four monogenic genes (LRRK2, PRKN, PINK1, and SNCA). Eight genes were associated with PD risk in the Polish population (GBA, TFAM, NFE2L2, MMP12, HLA-DRA, COMT, MAOB, and DBH). Multiplex ligation-dependent probe amplification and Sanger sequencing in PRKN, PINK1, DJ1, LRRK2, and SNCA revealed SNCA duplication in a 43-year-old Polish patient with PD examined by movement disorder specialists. CONCLUSION: Only a limited number of positive results have been reported in genes previously associated with PD in the Polish population. In the era of personalised medicine, it is important to report on genetic findings in specific populations.

Validation of the Polish version of the Unified Dyskinesia Rating Scale (UDysRS).

BACKGROUND: In 2008, the Movement Disorders Society published the Unified Dyskinesia Rating Scale (UDysRS). This has become the established tool for assessing the severity and disability associated with dyskinesia in patients with Parkinson's Disease (PD). We translated and validated the Polish version of the UDysRS, explored its dimensionality, and compared it to the Spanish version, which is the Reference Standard for UDysRS translations. MATERIAL AND METHODS: The UDysRS was translated into Polish by a team led by JS and GO. The back-translation, completed by colleagues fluent in both Polish and English who were not involved in the original translation, was reviewed and approved by the Executive Committee of the MDS Rating Scales Programme. Then the translated version of the UDysRS underwent cognitive pretesting, and the translation was modified based on the results. The approved version was considered to be the Official Working Document of the Polish UDysRS and was tested on 250 Polish PD patients recruited at movement disorder centres. Data was compared to the Reference Standard used for validating UDysRS translations. RESULTS: The overall factor structure of the Polish version was consistent with that of the Reference Standard version, as evidenced by the high Confirmatory Fit Index score (CFI = 0.98). The Polish UDysRS was thus confirmed to share a common factor structure with the Reference Standard. CONCLUSIONS: The Official Polish UDysRS translation is recommended for use in clinical and research settings. Worldwide use of uniform rating measures offers a common ground to study similarities and differences in disease manifestations and progression across cultures.